A new experimental pill helped adults with obesity or overweight lose substantial amounts of weight in a mid-stage clinical trial.
At the highest dose, participants lost an average of about 12 percent of their starting body weight over 36 weeks.
The drug, called aleniglipron, is being developed as a new type of GLP-1 treatment for obesity. The randomized phase II clinical trial was published in the journal Nature Medicine.
Robert Kushner, professor emeritus of medicine at Northwestern University Feinberg School of Medicine, was a co-author of the study. The research was supported by Structure Therapeutics, the company developing the drug.
GLP-1 medicines have changed obesity treatment in recent years. Well-known drugs in this group include semaglutide, which is sold under brand names including Wegovy for weight management.
GLP-1 is a hormone naturally released by the digestive system after eating. It sends signals that help control blood sugar and tells the brain that food has entered the body.
Medicines that act on this system can reduce appetite and help people feel full after eating less food. Over time, this can lead to meaningful weight loss for many patients.
Most widely known GLP-1 medicines are made from molecules similar to natural hormones and are commonly given by injection. Although these treatments can be highly effective, injections can be inconvenient or undesirable for some people.
Some injectable products also have storage requirements, and manufacturing these complex medicines in very large quantities can be challenging. Researchers have therefore been trying to develop simpler oral alternatives.
Aleniglipron takes a different approach. It is a small molecule made through chemical manufacturing rather than a peptide-based medicine.
Small-molecule medicines include many familiar tablets used for conditions such as high blood pressure. They can often be produced in large quantities and formulated as pills.
According to Kushner, aleniglipron can be taken with or without food. That could make daily treatment easier than oral medicines that require strict instructions about when a person can eat or drink.
The phase II trial included 230 adults with obesity or overweight at 38 medical centers in the United States. Their average age was about 50.
Participants were randomly assigned to receive aleniglipron or a placebo, which looked like the treatment but contained no active drug. Neither the participants nor the researchers directly involved knew who was receiving the real medicine during the blinded trial.
The researchers tested daily doses of 45, 90 and 120 milligrams. Instead of immediately giving participants the full dose, the amount was gradually increased every four weeks.
This gradual increase is commonly used with GLP-1 medicines because digestive side effects can be stronger when treatment begins. Giving the body time to adjust may improve tolerability.
After 36 weeks, participants taking 45 milligrams had lost an average of 9 percent of their starting body weight. Those receiving 90 milligrams lost about 10.7 percent.
The largest average reduction occurred in the 120-milligram group, where body weight fell by about 12.1 percent. By comparison, the placebo group lost only about 0.5 percent.
To put that into everyday terms, a person starting at 100 kilograms would lose roughly 12 kilograms with a 12 percent reduction. Individual results can differ considerably, so this example does not predict what would happen to every patient.
Digestive problems were the main side effects. These were generally described as mild to moderate and became less frequent as treatment continued.
Overall, 10.4 percent of participants stopped treatment. Importantly, researchers reported no cases of liver injury caused by the drug during the trial.
These safety findings are encouraging because liver problems have been an important concern for some experimental medicines. However, a study of 230 people lasting 36 weeks cannot identify every possible rare or long-term side effect.
The researchers plan to study aleniglipron in a larger phase III trial. They also intend to increase the dose more slowly in hopes of making treatment easier to tolerate.
Phase III trials are a crucial step in drug development. They usually include many more participants and provide stronger evidence about whether a medicine’s benefits outweigh its risks.
If the results remain positive, an oral small-molecule GLP-1 drug could expand treatment choices. Some patients who do not want injections may prefer a daily pill, and easier manufacturing could potentially help increase supply.
Still, several questions remain unanswered. The current trial lasted only 36 weeks, while obesity is a long-term condition that often requires treatment for years.
Researchers will need to learn whether weight loss continues, reaches a plateau or changes with longer treatment. They will also need to study what happens when patients stop taking the medicine.
The trial’s randomized, double-blind and placebo-controlled design is an important strength because it reduces several common sources of bias. The clear dose-related weight loss also supports the conclusion that aleniglipron itself produced much of the observed effect.
However, this was a phase II study designed partly to identify useful doses and assess safety. It does not yet provide the amount of evidence normally required for widespread approval and routine use.
The study’s industry funding should also be considered when interpreting the results. Company-supported drug trials are an essential part of medicine development, but independent review and larger confirmatory studies remain important.
Overall, the Nature Medicine findings make aleniglipron a promising candidate in the rapidly growing field of obesity medicines.
A once-daily pill producing average weight loss approaching 12 percent could be valuable, but phase III results will be needed to show whether its effectiveness and safety hold up in a much larger population.
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Source: Northwestern University.
